In mammalian lungs, airway smooth muscle cells (airway SMCs) are present in the proximal lung adjacent to bronchi and bronchioles, but are absent in the distal lung adjacent to terminal sacs that expand during gas exchange. Evidence suggests that this distribution is essential for the formation of a functional respiratory tree, but the underlying genetic mechanism has not been elucidated. In this study, we test the hypothesis that fibroblast growth factor 9 (Fgf9) signaling is essential to restrict SMC differentiation to the proximal lung. We show that loss of

Background Mammalian lung development consists of a series of precisely choreographed events that drive the progression from simple lung buds to the elaborately branched organ that fulfills the vital function of gas exchange. Strict transcriptional control is essential for lung development. Among the large number of transcription factors encoded in the mouse genome, only a small portion of them are known to be expressed and function in the developing lung. Thus a systematic investigation of transcription factors expressed in the lung is warranted. Results To enrich for genes that may be responsible for regional growth and patterning, we performed a screen using RNA in situ hybridization to identify genes that show restricted expression patterns in the embryonic lung. We focused on the pseudoglandular stage during which the lung undergoes branching morphogenesis, a cardinal event of lung development. Using a genome-scale probe set that represents over 90% of the transcription factors encoded in the mouse genome, we identified sixty-two transcription factor genes with localized expression in the epithelium, mesenchyme or both. Many of these genes have not been previously implicated in lung development. Conclusions Our findings provide new starting points for the elucidation of the transcriptional circuitry that controls lung development.

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